Predictive factors of severe infections in patients with systemic necrotizing vasculitides: data from 733 patients enrolled in five randomized controlled trials of the French Vasculitis Study Group.

OBJECTIVES: Infections remain a major cause of morbidity and mortality in systemic necrotizing vasculitides (SNV). We aimed to identify factors predicting severe infections (SI) in SNV. METHODS: Data from five randomized controlled trials (RCTs) enrolling 733 patients were pooled. The primary end point was the occurrence of SI, defined by the need of a hospitalization and/or intravenous anti-infectious treatment and/or leading to death. RESULTS: After a median follow-up of 5.2 (interquartile range 3-9.7) years, 148 (20.2%) patients experienced 189 SI, and 98 (66.2%) presented their first SI within the first 2 years. Median interval from inclusion to SI was 14.9 (4.3-51.7) months. Age ≥65 years (hazard ratio (HR) 1.49 [1.07-2.07]; P=0.019), pulmonary involvement (HR 1.82 [1.26-2.62]; P=0.001) and Five Factor Score ≥1 (HR 1.21 [1.03-1.43]; P=0.019) were independent predictive factors of SI. Regarding induction therapy, the occurrence of SI was associated with the combination of GCs and CYC (HR 1.51 [1.03-2.22]; P = 0.036), while patients receiving only GCs were less likely to present SI (HR 0.69 [0.44-1.07]; P = 0.096). Finally, occurrence of SI had a significant negative impact on survival (P<0.001). CONCLUSION: SI in SNV are frequent and impact mortality. Age, pulmonary involvement and Five Factor Score are baseline independent predictors of SI. No therapeutic regimen was significantly associated with SI but patients receiving glucocorticoids and CYC as induction tended to have more SI.

Successful treatments of polyarteritis nodosa cerebral vasculitis and recurrent E lizabethkingia meningoseptica septicaemia in a dialysis patient.

We report a case of cerebral vasculitis in a 31-year-old woman who presented with chronic kidney disease stage 5, labile hypertension and severe headaches. The diagnosis of cerebral vasculitis made on magnetic resonance angiography (MRA) and late diagnosis of polyarteritis nodosa were made by conventional CT angiography. Immunosuppression was complicated by recurrent septicaemia due to Elizabethkingia meningoseptica Treatment of the vasculitis resulted in marked improvement of MRA appearances, headaches and anxiety and stabilisation of blood pressure. The septicaemia required parenteral quinolone treatment and oral cotrimoxazole.

Cryptococcus neoformans meningoencephalitis in a patient with polyarteritis nodosa.

Case of 59-year-old male with chronic obstructive pulmonary disease and a number of comorbidities, who has developed meningoencephalitis caused by Cryptococcus neoformans var. grubii with polyarteritis nodosa diagnosed during hospitalization, was presented. Before evidence of meningoencephalitis, the patient was being treated with ketoconazole and low doses of fluconazole (200 mg/day) for alleged candidiasis. The dosage was increased (800 mg/day) following laboratory diagnosis of C. neoformans based on positive latex agglutination test and biochemical identification of encapsulated yeast isolated from the blood and CSF. Later, the yeast identification was confirmed by sequencing analysis. Owing to inadequate clinical response, fluconazole therapy was switched to voriconazole (400 mg/day) and later to intravenous amphotericin B (1.0 mg/kg per day). Despite of a temporary stabilization and improvement, which correlated with decline of cryptococcal antigen titers (from 1:1024 to 1:8), after 6 weeks, the patient's underlying condition deteriorated due to severe pancolitis and serious nosocomial bacterial infections. The patient died of multiorgan failure several days later. Our case demonstrates a possible connection between the development of life-threatening cryptococcosis and an autoimmune vasculitis disease and emphasizes that the outcome of the management of cryptococcal meningoencephalitis is highly dependent on early diagnosis, adequate treatment, including dosage, and last but not least control of underlying disease and risk factors.

Síndrome «humpy-backed» en cerdos en España / «Humpy-backed» pigs’ syndrome in Spain

El síndrome «humpy-backed» fue descrito en cerdos por primera vez en el Reino Unido en 1984. El síndrome ha sido observado en algunos países pero la etiología y la patogenia son todavía desconocidas. Este caso describe la aparición de cerdos con «humpy-backed» en la lechonera de una granja de 3.800 cerdas situada en el noreste de España. El problema afectó aproximadamente al 3% de la progenie semanal de una línea genética particular de la granja compuesta por 450 cerdas. La incidencia alcanzó picos del 9-11% en algunas semanas. Los lechones aparecían deprimidos, con pelaje hirsuto y deterioro físico progresivo. En la necropsia, a pesar de la apariencia de lordosis, no se detectaron alteraciones en los huesos y articulaciones de la columna vertebral. Microscópicamente se observó periarteritis linfoplasmocítica en corazón, bazo, intestino, hígado, riñón, músculo esquelético, pulmón y meninges. También se observó miocarditis y miositis linfoplasmocítica con degeneración de fibras musculares esqueléticas. La apariencia macroscópica de lordosis se relacionó con infiltrado celular inflamatorio multiorgánico. Se asoció a un problema de tipo genético de los animales afectados, aunque podría haber una posible implicación de circovirus porcino tipo 2 (PCV2) y el virus del síndrome reproductivo y respiratorio porcino (PRRS) en la patogenia del síndrome, debido a la seropositividad frente a los mismos detectada en la granja (AU)

«Humpy-backed» pigs’ syndrome was firstly described in the United Kingdom in 1984. The syndrome has been reported in a few countries, but the ethiology and pathogenesis remains unclear. This report describes the appearance of «humpy-backed» piglets aetiology in the nursery of a 3800-sow farm in Northeast Spain. The problem affected around 3% of the weekly offspring from one particular genetic line present on the farm composed of 450 sows. The incidence reached peaks of 9-11% in some weeks. The piglets appeared depressed, with rough hair coat and progressive clinical deterioration. In the necropsy, despite the appearance of lordosis, no defect in the bones and joint of the vertebral spine were detected. Lympho-plasmacytic periarteritis was observed in heart, spleen, gut, liver, kidney, skeletal muscle, lung and meninges. Lympho-plasmacytic myocarditis and skeletal myositis with muscular fibre degeneration was also observed. The macroscopic appearance of lordosis was associated with a multiorganic inflammatory cell infiltration. There was an association with the genetic background of the affected animals although seropositivity to porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) was also found in the farm, pointing to a possible implication of viral infection in the pathogenesis of the syndrome (AU)

What is the evidence for prophylactic antibiotic treatment in patients with systemic vasculitides?

PURPOSE OF REVIEW: Microbial factors are supposed to play an inducing and/or reactivating role in many of the idiopathic systemic vasculitides. This review evaluates the evidence that microbes are involved in the etiopathogenesis of the disease focusing on possibilities for antimicrobial intervention. RECENT FINDINGS: The clinical presentation of hepatitis B virus (HBV)-associated polyarteritis nodosa (PAN) is different from that of non-HBV-PAN and requires antiviral treatment. In hepatitic C virus (HCV)-associated autoimmune diseases, type 2 cryoglobulinemia is present in 52% of cases. Chronic nasal carriage of Staphylococcus aureus is related to endonasal activity of Wegener's granulomatosis and recurrent relapses, and prophylactic treatment with co-trimoxazole is effective in reducing relapse rate. SUMMARY: Patients with PAN should be tested for HBV, and patients with type 2 cryoglobulinemia for HCV. When tested positive, antiviral treatment should be considered. Patients with Wegener's granulomatosis should be tested for nasal carriage of S. aureus, and prophylactic treatment with co-trimoxazole should be considered in case of persistent endonasal activity of Wegener's granulomatosis together with S. aureus carriage. The efficacy of S. aureus elimination for preventing relapses of Wegener's granulomatosis should be evaluated.

[Juvenile cutaneous polyarteritis nodosa associated with streptococcal infection]. / Poliarterite nodosa cutânea infantil associada a infecção estreptocócica.

Polyarteritis nodosa is a rare vasculitis of small and medium arteries. It can occur in a systemic form with multi-organ involvement, or as a limited form confined to the skin, muscles, joints and peripheral nerves called cutaneous polyarteritis nodosa. Both forms are rare in adults and even more in children. The caues of this vasculitis remain unknown but some viruses and bacteria have been implicated, specially, Streptococcus. We present the case of a 6-year-old child who developed cutaneous polyarteritis nodosa following a probable streptococcal infection.

Successive development of cutaneous polyarteritis nodosa, leucocytoclastic vasculitis and Sweet's syndrome in a patient with cervical lymphadenitis caused by Mycobacterium fortuitum.

Mycobacterium fortuitum is a rapidly growing mycobacterium found in soil and water throughout the world. It can cause diseases in immunocompetent patients, usually resulting in localized skin and soft tissue infections. Cervical lymphadenitis caused by M. fortuitum is rare. We report a 46-year-old woman in whom skin lesions of cutaneous polyarteritis nodosa, leucocytoclastic vasculitis and Sweet's syndrome had successively developed before the diagnosis of cervical lymphadenitis caused by M. fortuitum was made. The skin lesions responded to colchicine and systemic corticosteroids but recurred intermittently. After establishment of the diagnosis, she received treatment with clarithromycin and ciprofloxacin. The cervical lymph nodes decreased in size 6 months later and no more new skin lesions were found.

[A case of adult polyarteritis nodosa associated with fulminant group A streptococcal infection].

We report a case of adult polyarteritis nodosa (PN) associated with group A streptococcal infection. A 37-year-old male had suffered from high fever, polyarthralgia, myalgia, and exanthema following pharyngalgia. He was admitted to the hospital because of cutaneous ulcers and necrosis making the general condition rapidly poor. A serological streptococcal test showed a marked increase in antistreptlysin-O (ASO) and a positive reaction to C polysaccharide, suggesting fulminant streptococcal infection. Various antibiotics including penicillin agents were administered. However improvement and exacerbation were repeatedly noted. In the hospital course peripheral neuritis and subcutaneous nodes in upper extremities developed. Biopsy specimen of subcutaneous nodes revealed necrotizing angiitis. Administration of a steroid achieved complete response, and the symptoms, inflammatory reaction, and ASO level improved. While the dose of the steroid was tapered gradually, recurrence was noted. However, increasing the dose finally resulted in relief. During the 2-year follow-up, there was a correlation between the ASO level and inflammatory reaction.

Cutaneous polyarteritis nodosa after streptococcal necrotizing fasciitis.

Polyarteritis nodosa (PAN) is a necrotizing arteritis of small and medium-sized vessels. It may present with hypertension and/or renal insufficiency. Peripheral neuropathy, myopathy, joint pains, testicular pain, and ischemic myalgias may also be seen. Gastrointestinal involvement may lead to gangrene of the bowel, peritonitis, perforation, intra-abdominal hemorrhage, and pancreatitis. The cutaneous manifestations include tender subcutaneous nodules grouped along the course of superficial arteries of the lower extremities, with or without an overlying livedo reticularis. Although multisystem involvement is characteristic, sometimes only one organ or system may be involved. Associations with viral hepatitis (both B and C) and streptococcal infection have been established for PAN. Recurrent strep infections of the upper respiratory tract, streptococcal glomerulonephritis and rheumatic fever have previously been linked to PAN. This report extends the spectrum of associated streptococcal infections to include necrotizing fasciitis.

Severe abdominal involvement as the initial manifestation of cutaneous polyarteritis nodosa in a young girl.

We report a young girl who developed ingravescent intestinal symptoms as the first manifestation of cutaneous polyarteritis nodosa (PAN) while the typical skin nodules developed later during the disease course. Cutaneous PAN predominantly affects children and presents with crops of painful skin nodules in the medial aspect of the foot, often preceded by sore throat. Visceral manifestations including gut involvement are commonly associated with the classical form of PAN while they are rarely reported in the cutaneous form. In our patient the severity of the abdominal symptoms required a laparoscopy, which revealed diffuse erythematosus swelling of the intestine on the serosal side. The administration of penicillin and steroids was followed by a dramatic improvement in the disease course. Chronic anterior uveitis developed 4 months after the disease onset and responded to local treatment. At a 2-year follow-up the girl is in good condition under prophylaxis with benzathine-penicillin with no recurrence of the illness. Our case confirms that cutaneous PAN is often related to streptococcal infection, and suggests that ASO titers should be determined in children with vasculitides to ensure a timely diagnosis and treatment of the condition if present.

Juvenile relapsing periarteritis nodosa and streptococcal infection.

Classic polyarteritis nodosa is a multisystem inflammatory disease associated with necrotizing vasculitis of small and medium arteries. In most cases, the causes of polyarteritis nodosa remain unknown, but viruses (HBV, HCV, HIV) and microbes (especially streptococcus) have been considered as etiologic or contributing factors. A 13-year-old boy was admitted with fever, skin lesions, polyarthritis and muscle involvement. A muscle biopsy demonstrated a necrotizing vasculitis and antistreptolysin titre was tremendously increased. His condition improved following the administration of oral steroids but he experienced relapses 5 and 12 years later when penicillin withdrawal was attempted. The flares were accompanied by a major increase of antistreptolysin titre and response to corticosteroid was obtained. He is currently 38 years old and he remains well on prophylactic penicillin. Polyarteritis nodosa in children may occur after a streptococcal infection. It may be prudent to consider penicillin prophylaxis in patients with periarteritis nodosa when a streptococcal etiology is documented or highly suspected.

Ehrlichiosis associated vasculitis.

OBJECTIVE: To test the hypothesis that some cases of primary vasculitis are caused by ehrlichiosis. DESIGN: A retrospective case study and serological analysis of stored sera. SETTING: University hospital. SUBJECTS: Fifty-five patients discharged with any type of vasculitis over a 6-year period. MAIN OUTCOME MEASURES: Serology for human monocytic ehrlichiosis, and the human granulocytic ehrlichiosis agent, and polymerase chain reaction (PCR) analysis of biopsy specimens. RESULTS: Three patients (5.5%) had titres of 1 : 128 or higher against E. chaffeensis; none was positive for the human granulocytic ehrlichiosis agent. Skin biopsies of these patients showed lesions compatible with polyarteritis nodosa, allergic purpura and unspecified vasculitis. PCR analysis of the biopsies was unrevealing. CONCLUSIONS: Infection with human monocytic ehrlichiosis may underlie some forms of vasculitis. If confirmed, these findings may help identify patients with vasculitis who would benefit from antibiotic treatment.

Pneumocystis carinii pneumonia in patients with connective tissue diseases: the role of hospital experience in diagnosis and mortality.

OBJECTIVE: Pneumonia due to Pneumocystis carinii has been increasingly reported in patients with connective tissue diseases, but the frequency of this complication is not known. We sought to determine the frequency of P carinii pneumonia (PCP) in patients with connective tissue diseases, and to determine the role that a hospital's acquired immunodeficiency syndrome (AIDS)-related experience may have in the diagnosis of PCP in these patients. METHODS: We used a state hospitalization registry to identify all patients with PCP and either rheumatoid arthritis, systemic lupus erythematosus, Wegener's granulomatosis, polymyositis, dermatomyositis, polyarteritis nodosa, or scleroderma who had an emergent or urgent hospitalization in California from 1983 to 1994. We compared patient and hospital characteristics between these patients and patients with connective tissue diseases hospitalized with other types of pneumonia. RESULTS: Two hundred twenty-three patients with connective tissue diseases were diagnosed with PCP in the 12-year study period. The frequency of PCP ranged from 89 cases/10,000 hospitalizations/year in patients with Wegener's granulomatosis to 2 cases/10,000 hospitalizations/year in patients with rheumatoid arthritis. Compared with 5,457 patients with connective tissue diseases and pneumonia due to other organisms, patients with PCP were more likely to be younger, to be male, to have private medical insurance, and to have systemic lupus erythematosus, Wegener's granulomatosis, inflammatory myopathy, or polyarteritis nodosa rather than rheumatoid arthritis, and were less likely to be African American. Hospital size, teaching status, urban/rural location, proportion of admissions due to AIDS or PCP, and proportion of patients with pneumonia undergoing bronchoscopy were each associated with the likelihood of diagnosis of PCP in univariate analyses, but only the number of patients with PCP being treated at a hospital (odds ratio [OR] 1.03 for each additional 10 cases/year, 95% confidence interval [95% CI] 1.01-1.05) was associated with the likelihood of diagnosis of PCP in multivariate analyses. Patients were also somewhat more likely to be diagnosed with PCP if there had previously been a case of PCP in a patient with a connective tissue disease at the same hospital (OR 135, 95% CI 0.98-1.85). In-hospital mortality was 45.7%, and was unrelated to hospital characteristics. CONCLUSION: PCP is an uncommon, but often fatal, occurrence in patients with connective tissue disease. A hospital's prior experience with patients with PCP is associated with the likelihood that this condition is diagnosed in patients with connective tissue diseases who present with pneumonia, suggesting that diagnostic suspicion is an important factor in the correct identification of affected patients.

Relapsing cutaneous polyarteritis nodosa associated with streptococcal infections.

BACKGROUND: Polyarteritis nodosa is an aggressive, often fatal form of vasculitis associated with multi-organ involvement. Cutaneous polyarteritis nodosa is purported to be a more benign form of this disorder with involvement limited to the skin. METHODS: The identification of a female patient from childhood to adulthood documenting repeated episodes of cutaneous polyarteritis nodosa following bouts of recurrent streptococcal pharyngitis. RESULTS: Repeated bouts of streptococcal pharyngitis at ages 11, 28, and 33 years were followed by episodes of cutaneous polyarteritis nodosa, documented by histopathologic skin changes and clinical presentation, and confirmed by therapeutic management. CONCLUSIONS: Various infectious and non-infectious conditions have been linked both to the initiation and relapse of this disease. We describe a patient with recurrent episodes of cutaneous polyarteritis nodosa spanning a period of over 20 years with each episode appearing to be linked to a prior streptococcal infection.

Long-term follow-up of juvenile-onset cutaneous polyarteritis nodosa associated with streptococcal infection.

Polyarteritis nodosa (PAN) is a multisystem inflammatory disease associated with necrotizing vasculitis of small and medium arteries. Although predominantly an adult disease, PAN is well described in children. It can occur in a systemic form with manifestations in skin, joints, heart, nervous system, gastrointestinal tract, lungs and kidneys, and a limited form in which disease is confined to the skin, muscles, joints and peripheral nerves. In either case, streptococcal infection has been implicated by a positive throat swab or a significant increase in either antistreptolysin O (ASOT) or antihyaluronidase titres. The limited form is thought to run a benign course, but little has been written about its long-term outcome. We describe two patients who developed a cutaneous vasculitis following a probable streptococcal infection. Both have run a relapsing and remitting course with significant elevations of ASOT and in one, at least, prophylactic penicillin has had a strikingly beneficial effect. In both patients, the disease seems to have receded during childhood, only to recur, retaining its original form, in adult life. Their current ages are 22 and 19 yr, respectively.